Himadri S Gupta

Queen Mary, University of London | QMUL · School of Engineering and Materials Science

The bone-cartilage unit (BCU) is a universal feature in diarthrodial joints, which is mechanically-graded and subjected to shear and compressive strains. Changes in the BCU have been linked to osteoarthritis (OA) progression. Here we report existence of a physiological internal strain gradient (pre-strain) across the BCU at the ultrastructural scal...

The structure and mechanical properties of the stomatopod dactyl club have been studied extensively for its extreme impact tolerance, but a systematic in situ investigation on the multiscale mechanical responses under high-speed impact has not been reported. Here the full dynamic deformation and crack evolution process within projectile-impacted da...

Fibrotic scarring is prevalent in a range of collagenous tissue disorders. Understanding the role of matrix biophysics in contributing to fibrotic progression is important to develop therapies, as well as to elucidate biological mechanisms. Here, we demonstrate how microfocus small-angle X-ray scattering (SAXS), with in situ mechanics and correlati...

Mutable connective tissues of the sea cucumbers’ dermis can assume three different mechanical states (soft, standard and stiff) according to the chemical changes in the water. There is broad consensus that variable cross-linking of the extracellular matrix is responsible for such changes. This paper uses Small-angle X-ray Scattering (SAXS) measurem...

The bone-cartilage interface (BCI) and underlying calcified plate is a universal feature in diarthrodial joints. The BCI is an important mechanically-graded interface subjected to shear and compressive strains, and changes at the BCI have been linked to osteoarthritis progression. Here we report the existence of a physiological internal strain grad...

Biomechanical changes to the collagen fibrillar architecture in articular cartilage are believed to play a crucial role in enabling normal joint function. However, experimentally there is little quantitative knowledge about the structural response of the Type II collagen fibrils in cartilage to cyclic loading in situ, and the mechanisms that drive...

The structure and mechanical properties of the stomatopod dactyl club have been extensively studied for its extreme impact tolerance, but a systematic, in situ , investigation on the multiscale mechanical responses under high-speed impact has not been reported. Here we reveal the full dynamic deformation and crack evolution process within projectil...

Small-angle X-ray scattering (SAXS) is an effective characterization technique for multi-phase nanocomposites. The structural complexity and heterogeneity of biological materials require the development of new techniques for the 3D characterization of their hierarchical structures. Emerging SAXS tomographic methods allow reconstruction of the 3D sc...

Metabolic bone diseases have an impact on the multi-scale structure of bone and its mechanical properties. This study aims to conduct quantitative analysis of the link between specific material-level changes and mechanical alterations of bone tissue. We combine several scanning probe methods with an analytical multiscale model to investigate these...

Objective Cartilage health is maintained in response to a range of mechanical stimuli including compressive, shear and tensile strains and associated alterations in osmolality. The osmotic-sensitive ion channel Transient Receptor Potential Vanilloid 4 (TRPV4) is required for mechanotransduction. Mechanical stimuli inhibit interleukin-1β (IL-1β) med...

Dynamic soft materials that have the ability to expand and contract, change stiffness, self-heal or dissolve in response to environmental changes, are of great interest in applications ranging from biosensing and drug delivery to soft robotics and tissue engineering. This book covers the state-of-the-art and current trends in the very active and ex...

Dynamic soft materials that have the ability to expand and contract, change stiffness, self-heal or dissolve in response to environmental changes, are of great interest in applications ranging from biosensing and drug delivery to soft robotics and tissue engineering. This book covers the state-of-the-art and current trends in the very active and ex...

Determining multiscale, concurrent strain, and deformation mechanisms in hierarchical biological materials is a crucial engineering goal, to understand structural optimization strategies in Nature. However, experimentally characterizing complex strain and displacement fields within a 3D hierarchical composite, in a multiscale full-field manner, is...

Glucocorticoid (or steroid) induced osteoporosis (GIOP) is the leading form of secondary osteoporosis, affecting up to 50% of patients receiving chronic glucocorticoid therapy. Bone quantity (bone mass) changes in GIOP patients alone are inadequate to explain the increased fracture risk, and bone material changes (bone quality) at multiple levels h...

As bone is used in a dynamic mechanical environment, understanding the structural origins of its time-dependent mechanical behaviour - and the alterations in metabolic bone disease - is of interest. However, at the scale of the mineralized fibrillar matrix (nanometre-level), the nature of the strain-rate dependent mechanics is incompletely understo...

The cuticle of stomatopod is an example of a natural mineralized biomaterial, consisting of chitin, amorphous calcium carbonate and protein components with a multiscale hierarchical structure, and forms a protective shell with high impact resistance. At the ultrastructural level, cuticle mechanical functionality is enabled by the nanoscale architec...

Structural and associated biomechanical gradients within biological tissues are important for tissue functionality and preventing damaging interfacial stress concentrations. Articular cartilage possesses an inhomogeneous structure throughout its thickness, driving the associated variation in the biomechanical strain profile within the tissue under...

Insect cuticle has drawn a lot of attention from engineers because of its multifunctional role in the life of insects. Some of these cuticles have an optimal combination of lightweight and good mechanical properties, and have inspired the design of composites with novel microstructures. Among these, beetle elytra have been explored extensively for...

Glucocorticoid-induced osteoporosis (GIOP) is a major secondary form of osteoporosis, with the fracture risk significantly elevated - at similar levels of bone mineral density - in patients taking glucocorticoids compared with non-users. The adverse bone structural changes at multiple hierarchical levels in GIOP, and their mechanistic consequences...

The mutable collagenous tissue (MCT) of echinoderms (e.g. sea cucumbers, starfish and sea urchins) is unique because of its ability to 'switch' mechanical states rapidly and reversibly - from stiff to soft and vice versa. This kind of tissue in humans, for example, in skin, tendons and ligaments, does not have this property. So what are the molecul...

Modelling the mechanical behaviour of soft tissues like tendon, ligament, skin and cartilage requires a knowledge of the structural and mechanical properties of the constitutive elements. These tissues have a hierarchical architecture from the molecular to the macroscopic scale, and are composites of different molecular building blocks. Here we fir...

Articular cartilage is a natural biomaterial whose structure at the micro- and nanoscale is critical for healthy joint function and where degeneration is associated with widespread disorders such as osteoarthritis. At the nanoscale, cartilage mechanical functionality is dependent on the collagen fibrils and hydrated proteoglycans that form the extr...

Determining the in situ 3D nano-and microscale strain and reorientation fields in hierarchical nanocomposite materials is technically very challenging. Such a determination is important to understand the mechanisms enabling their functional optimization. An example of functional specialization to high dynamic mechanical resistance is the crustacean...

The body wall of starfish is composed of magnesium calcite ossicles connected by collagenous tissue and muscles and it exhibits remarkable variability in stiffness, which is attributed to the mechanical mutability of the collagenous component. Using the common European starfish Asterias rubens as an experimental animal, here we have employed a vari...

The high toughness and work to fracture of hierarchical composites, like antler bone, involve structural mechanisms at the molecular, nano-, and micro scales, which are not completely explored. A key characteristic of the high energy absorption of such materials is the large hysteresis during cyclic loading, but its origin remains unknown. In situ...

Significance Collagen plays crucial biomechanical roles in a wide array of animal tissues, but its mechanical properties remain largely static over short timescales. However, echinoderms (sea cucumbers, starfish) are striking exceptions to this rule, having “mutable collagenous tissue” with changeable mechanical properties, enabling complex locomot...

The complex hierarchical structure in biological and synthetic fibrous nanocomposites entails considerable difficulties in the interpretation of the crystallographic texture from diffraction data. Here, we present a novel reconstruction method to obtain the 3D distribution of fibres in such systems. An analytical expression is derived for the diffr...

3D reconstruction of Crh− 120/+ tibia mid diaphysis showing reduced vascular network and disturbed distribution of osteocyte lacunae. Resorption cavities can be observed along the entire length of the bone and they are segmented with red color for better visualization.

3D reconstruction of WT tibia mid diaphysis showing vascular network and distribution of osteocyte lacunae.

Multiscale alterations in bone matrix quality increased fragility in steroid induced osteoporosis

A serious adverse clinical effect of glucocorticoid steroid treatment is secondary osteoporosis, enhancing fracture risk in bone. This rapid increase in bone fracture risk is largely independent of bone loss (quantity), and must therefore arise from degradation of the quality of the bone matrix at the micro- and nanoscale. However, we lack an under...

Naturally occurring composite structures like antler bone and nacre have a highly ordered structural design at the nanoscale. Natures’ successful architecture has attracted a widespread interest in mimicking such systems artificially, the goal being to design tough composite materials with adaptable mechanical properties. Here we report results on...

Integrative and comparative analyses of biomaterials systems offer the potential to reveal conserved elements that are essential for mechanical function. The approach also affords the opportunity to identify variation in designs at multiple length scales, enabling the delineation of a range of parameters for creating precisely tuned biomimetic mate...

Antler bone displays considerable toughness through the use of a complex nanofibrous structure of mineralized collagen fibrils (MCFs) bound together by non-collagenous proteins (NCPs). While the NCP regions represent a small volume fraction relative to the MCFs, significant surface area is evolved upon failure of the nanointerfaces formed at NCP-co...

Bone diseases such as osteoporosis and rickets cause significant reduction in both bone quantity and quality, leading to mechanical abnormalities at the organ level. While the reduction of bone quantity can be assessed using existing clinical tools like DXA and pQCT, there is little quantitative knowledge of how altered bone quality in diseased bon...

In situ synchrotron X-ray scattering and diffraction, in combination with micromechanical testing, can provide quantitative information on the nanoscale mechanics of biomineralized composites, such as bone, nacre, and enamel. Due to the hierarchical architecture of these systems, the methodology for extraction of mechanical parameters at the molecu...

The inelastic deformability of the mineralised matrix in bones is critical to their high toughness, but the nanoscale mechanisms are incompletely understood. Antler is a tough bone type, with a nanostructure composed of mineralised collagen fibrils ∼100nm diameter. We track the fibrillar deformation of antler tissue during cyclic loading using in s...

The plasma protein fetuin-A/alpha2-HS-glycoprotein (genetic symbol Ahsg) is a systemic inhibitor of extraskeletal mineralization, which is best underscored by the excessive mineral deposition found in various tissues of fetuin-A deficient mice on the calcification-prone genetic background DBA/2. Fetuin-A is known to accumulate in the bone matrix th...

Schematic of sample preparation. (A). Femora of mice were sectioned along the anteriorposterior axis (as seen by micro-CT) scale bar: 3 mm (B). Cortical bone from the mid-diaphysis of each sample were further sectioned (C). Sectioning and polishing along the longitudinal-tangential plane (D). Laser microdissection was used to further section the sa...

Determining the fibrillar strain from SAXS measurements. (A) Image of the meridional collagen SAXS pattern from Fit2D (B) Radial integration of the meridional collagen pattern produces an intensity profile with respect to Q-space showing the 1st, 2nd, and 3rd order reflections (C) Fibrillar strain can be measured from the percent change in position...

Tibia morphology and mineralization in wildtype (Ahsg +/+) and fetuin-A deficient (Ahsg−/−) mice. The mean calcium content in tibias of Ahsg −/− mice was increased in comparison to wildtype mice as judged by quantitative backscattered electron imaging of the enlarged areas shown in the middle panels. Ash weight of tibia halves (shown in the top pan...

Distal femur growth plate morphology and mineralization in wildtype (A, C, E) and fetuin-A deficient (B, D, F) mice. These representative samples show higher numbers of bone bridges and more mineralization in the growth plate of fetuin-A deficient mice than wildtype mice. (TIF)

The egg capsules of marine prosobranch gastropods, commonly know as whelks, function as a protective encapsulant for whelk embryos in wave-swept marine environments. The proteinaceous sheets comprising the wall of whelk egg capsules (WEC) exhibit long-range reversible extensibility with a hysteresis of up to 50 per cent, previously suggested to res...

The complex structural organization of the aortic valve (AV) extracellular matrix (ECM) enables large and highly nonlinear tissue level deformations. The collagen and elastin (elastic) fibers within the ECM form an interconnected fibrous network (FN) and are known to be the main load-bearing elements of the AV matrix. The role of the FN in enabling...

Metabolic bone disorders such as rickets are associated with altered in vivo muscular force distributions on the skeletal system. During development, these altered forces can potentially affect the spatial and temporal dynamics of mineralised tissue formation, but the exact mechanisms are not known. Here we have used a murine model of hypophosphate...

Bone diseases such as rickets and osteoporosis cause significant reduction in bone quantity and quality, which leads to mechanical abnormalities. However, the precise ultrastructural mechanism by which altered bone quality affects mechanical properties is not clearly understood. Here we demonstrate the functional link between altered bone quality (...

A setup is described where an individual electrospun polyamide fiber is attached to an atomic force microscope (AFM) tip and structural information collected with synchrotron micro Fourier transform infrared spectroscopy (μFT-IR). The combination of AFM and synchrotron μFT-IR therefore highlights the potential for recording structure-mechanical pro...

The complex structure of bone requires a structural description of the material at different hierarchical levels. At the micrometer level, collagen fi bril orientation and osteocyte network architecture can be described by different light microscopy methods. However, further investigation of the nanostructure of bone requires high-resolution techni...

The mechanical behaviour of hierarchically structured soft biological tissues like tendon and cartilage shows time-dependent properties. The origin of this phenomenon is undoubtedly related to the nano- and microscale levels of structural hierarchy, but the exact mechanism is not known. Understanding this phenomenon could help us understand normal...

Bone and nacre are the most-known biological hard tissues to materials researchers. Although highly mineralized, both bone and nacre are amazingly tough and exhibit remarkable inelasticity, properties that are still beyond the reach of many modern ceramic materials. Very interestingly, the two hard tissues seem to have adopted totally different str...

The lignin content and the mechanical properties of lignifying and fully lignified spruce tracheid secondary cell walls were determined using UV microscopy and nano-indentation, respectively. The average lignin content of developing tracheids was 0.10 g·g–1, as compared with 0.21 g·g–1 in mature tracheids. The modulus of elasticity of developing ce...

The remarkable mechanical properties of bone are due to its hierarchical structure which is optimized at all levels of hierarchy. At the lowest level, bone is a nanocomposite of collagen and mineral particles. The quality of this material is crucial for the mechanical performance of bone as a whole. In this chapter we review the structure and compo...

Current world technologies and environments rely in large measure upon a growing need for the development of new structural materials with high strength and durability, toughness, light weight, low cost, and complete recyclability. Such materials may be derived synthetically, but Nature has evolved efficient strategies, exemplified in the mineraliz...

Tendon is a hydrated multi-level fibre composite, in which time-dependent behaviour is well established. Studies indicate significant stress relaxation, considered important for optimising tissue stiffness. However, whilst this behaviour is well documented, the mechanisms associated with the response are largely unknown. This study investigates the...

The rational synthesis, comprehensive characterization, and mechanical and micromechanical properties of a calcium phosphate cement are presented. Hydroxyapatite cement biomaterial was synthesized from reactive sub-micrometer-sized dicalcium phosphate dihydrate and tetracalcium phosphate via a dissolution-precipitation reaction using water as the l...

Journal article